Levetiracetam has a time- and stimulation-dependent effect on synaptic transmission

We recently reported that rodent hippocampal slices incubated with levetiracetam for 3h had altered responses to repetitive stimulation and reduced neurotransmitter release. However, our experiments failed to determine the actual time course of diminished transmission in individual slices followed over time. We have now been able to record from the same slices for up to 3h to determine the latency of the levetiracetam effect after the onset of exposure. Within 30 min of levetiracetam exposure, the later field potentials of a burst were reduced. Between 60 and 180 min the relative size of later field potentials remained stable. Similar time-dependent reductions were not seen in control slices or in slices exposed to the inactive levetiracetam isomer UCB L060. These new results establish a clear time dependence of the levetiracetam effect, even in vitro, and are best explained by levetiracetam acting within neurons to alter synaptic vesicle release.